This Competitive Revision (NOT-OD-09-058;NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications) proposes to expand the scope of a currently funded project (R01DA023188) exploring the use of D-Cycloserine in facilitating extinction of response to cocaine-related cues by adding fMRI procedures (cocaine cue-induced BOLD fMRI, morphometric and volumetric MRI) before and after repeated trials of cocaine cue exposure. We hypothesize that there will be greater cocaine-cue induced activation in the prefrontal cortex, cingulate cortex, ventral striatum, amygdala and nucleus accumbens during the pre-extinction fMRI session as compared to the post-extinction fMRI session. Additionally, we hypothesize that there will be greater neutral-cue induced activation in the thalamus and amygdala during the post-extinction fMRI session as compared to the pre-extinction fMRI session. The addition of a BOLD fMRI component to this carefully controlled study of cocaine-cue extinction will accelerate and enhance the science of the parent proposal by allowing exploration of the neural circuitry activated in response to cocaine cues and alterations that occur after extinction of response to cocaine cues. Increased knowledge about neural processes involved in extinction could have clear therapeutic implications by providing empirical evidence to guide the search for therapeutic strategies which might be useful in reducing cue salience, facilitating cue extinction, or improving inhibitory control in cocaine-dependent individuals. Furthermore, the proposed project will provide economic stimulation by allowing for the hiring of additional staff for patient recruitment, protocol operation, and neuroimaging data analysis. PUBLIC HEALTH RELEVANCE: Cocaine-related environmental cues are likely to be involved in relapse. This study will add neuroimaging to an ongoing study of a pharmacologic intervention that may decrease the response to cocaine cues. Knowledge of the brain circuitry involved in craving may be important for developing treatments for cocaine dependence.